title: The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice.
abstract: Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University, Atlanta, Georgia; and.
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Koga
authors.forename: Niels
authors.initials: N
authors.lastname: Engberding
authors.forename: Anna E
authors.initials: AE
authors.lastname: Dikalova
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Chang
authors.forename: Bonnie
authors.initials: B
authors.lastname: Seidel-Rogol
authors.forename: James S
authors.initials: JS
authors.lastname: Long
authors.forename: Bernard
authors.initials: B
authors.lastname: Lassègue
authors.forename: Hanjoong
authors.initials: H
authors.lastname: Jo
authors.forename: Kathy K
authors.initials: KK
authors.lastname: Griendling
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan; D014657:Vasculitis / Q000503:physiopathology / Q000517:prevention & control*; D000099176:Noggin Protein
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D017382:Reactive Oxygen Species; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000099176:Noggin Protein
keywords: bone morphogenic protein; diabetes; inflammation; noggin; valsartan